Increase of Choline Acetyltransferase by Colchicine in Primary Cell Cultures of Spinal Cord

Abstract: Colchicine (5–10 μ M ) increased choline ace-tyltransferase (ChAT) activity 5–10-fold and suppressed acetylcholinesterase (AChE) and glutamate decarboxylase (GAD) activities to 30% and 50%, respectively, of the levels of control cells in mouse spinal cord cells cultured for several days. The synthesis of radiolaheled acetylcholine (ACh) from ¹⁴C]choline was also enhanced 4.6-fold, although the uptake of ¹⁴C]choline into cells was decreased to 80% of control level. Neither the incorporation of ³H]Ieucine into protein nor the total amount of protein was increased by colchicine. Vinblastine also increased ChAT activity while cytochalasin B was not effective. Immunochemical titration study revealed that the increase of ChAT activity by colchicine was due to the accumulation of ChAT molecules. Co-culture of spinalcord cells with skeletal muscle markedly stimulated ChAT activity, and the addition of colchicine to the co- cultures showed greater than additive effect. These observations indicate that colchicine increases ChAT molecules in a specific manner, that the stimulatory effect of colchicine on ChAT activity is possibly mediated via the interaction with microtubules, and that the increase of ChAT activity is based on a mechanism different from that of co-cultures with skeletal muscle cells.